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Baricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis.We conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti-tumor necrosis factor α monoclonal antibody) every other week. End-point measures evaluated after adjustment for multiplicity included 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) (the primary end point), the Disease Activity Score for 28 joints (DAS28), the Health Assessment Questionnaire-Disability Index, and the Simplified Disease Activity Index at week 12, as well as radiographic progression of joint damage as measured by the van der Heijde modification of the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating greater structural joint damage) at week 24.More patients had an ACR20 response at week 12 with baricitinib than with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary objectives were met, including inhibition of radiographic progression of joint damage, according to the mTSS at week 24 with baricitinib versus placebo (mean change from baseline, 0.41 vs. 0.90; P<0.001) and an increased ACR20 response rate at week 12 with baricitinib versus adalimumab (70% vs. 61%, P=0.014). Adverse events, including infections, were more frequent through week 24 with baricitinib and adalimumab than with placebo. Cancers were reported in five patients (two who received baricitinib and three who received placebo). Baricitinib was associated with reductions in neutrophil counts and increases in levels of creatinine and low-density lipoprotein cholesterol.In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358 .).

Original publication

DOI

10.1056/nejmoa1608345

Type

Journal article

Journal

The New England journal of medicine

Publication Date

02/2017

Volume

376

Pages

652 - 662

Addresses

From the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences and the Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom (P.C.T.); the Rebecca MacDonald Centre, Mount Sinai Hospital, University of Toronto, Toronto (E.C.K.); Leiden University Medical Center, Leiden, the Netherlands (D.H.); Brigham and Women's Hospital, Boston (M.E.W.); Instituto Reumatológico Strusberg, Córdoba, Argentina (L.C.M.); Centro de Investigacion Clinica Especializada, Mexico City (J.R.G.); Ryazan Regional Clinical Cardiology Dispensary, Ryazan, Russia (S.Y.); Eli Lilly, Indianapolis (T.I., S. Beattie, V.A., C.G., T.R., D.S., W.L.M., S. de Bono); and AstraZeneca K.K., Osaka (K.E.), and the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu (Y.T.) - both in Japan.

Keywords

Joints, Humans, Arthritis, Rheumatoid, Sulfonamides, Azetidines, Methotrexate, Antirheumatic Agents, Protein Kinase Inhibitors, Radiography, Drug Therapy, Combination, Administration, Oral, Double-Blind Method, Adult, Middle Aged, Female, Male, Janus Kinases, Adalimumab